[Ca²⁺](i) signaling in pregnant human myometrium

The purpose of the present study was to determine the changes in intracellular ionized calcium concentration ([Ca²⁺](i)) or [Ca²⁺](i) sensitivity accompanying spontaneous and agonist-induced contraction of human myometrium at term pregnancy, as well as to quantify the response to three prototypical agonists: 1) oxytocin, 2) vasopressin, and 3) phenylephrine. Uterine biopsies were obtained at the time of cesarean section from patients who delivered at or near full-term gestation. These preparations were used to measure isometric force development and [Ca²⁺](i) levels with the luminescent calcium indicator aequorin. Concentration-response relationships were determined with respect to isometric force development in the presence of the agonist. [Ca²⁺](i)-force relationships were determined with respect to spontaneous phasic contractions, as well as agonist-induced phasic and tonic contractions. The results provide evidence that the phasic nature of term human myometrium is due to 1) the resting [Ca²⁺](i) level being less than the calcium threshold for contractions and 2) the inability of the tissue to maintain high [Ca²⁺](i) levels for prolonged periods of time. In addition, calcium-independent mechanisms of regulation were suggested by the relatively minor calcium sensitizing action of oxytocin and the observation that relaxation of tonic contractions preceded the fall in [Ca²⁺](i) levels.